Effects of interferon treatment on liver histology and allograft rejection in patients with recurrent hepatitis C following liver transplantation

Liver Transpl. 2004 Jul;10(7):850-8. doi: 10.1002/lt.20189.


Recurrent hepatitis C after liver transplantation remains a significant cause of graft loss and retransplantation. Although treatment of recurrent hepatitis C with interferon-based regimens has become widely accepted as safe and can lead to sustained virologic clearance of hepatitis C virus (HCV) RNA, long-term histologic improvement and the risk of precipitating graft rejection remain controversial. The present study is a retrospective evaluation of the clinical and histological consequences of treating recurrent hepatitis C with interferon-based therapy in a selected group of liver transplant recipients. Twenty-three liver transplant recipients with recurrent hepatitis C and histologic evidence of progressive fibrosis completed at least 6 months of interferon, 83% of whom received pegylated-interferon alpha-2b; only 4 tolerated ribavirin. Overall, 11 patients (48%) had undetectable HCV RNA at the end of 6 months of treatment. Of these patients, 3 remained HCV RNA-negative on maintenance interferon monotherapy for 33 months, and the other 8 (35%) completed treatment and remained HCV RNA-undetectable 24 weeks after discontinuation of interferon. Overall necroinflammatory activity in liver biopsies obtained 2 years after HCV RNA became undetectable decreased significantly (7.73 +/- 2.37 vs. 5.64 +/- 2.94 units before and after treatment, respectively; P =.016). However, 5 of these 11 patients had no histologic improvement in follow-up liver histology. Liver biopsies in the 12 nonresponders demonstrated disease progression. Of the 23 patients treated with interferon, 8 (35%) had evidence of acute or chronic rejection on posttreatment liver biopsy, most of whom had no previous history of rejection (P <.01 for comparison of pretreatment and posttreatment prevalence of histologic rejection), and 2 experienced graft loss from chronic rejection, requiring retransplantation. In conclusion, interferon treatment of recurrent hepatitis C does not consistently improve histologic disease after virologic response, and it may increase the risk of allograft rejection.

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biopsy
  • Genotype
  • Graft Rejection / epidemiology*
  • Graft Rejection / pathology
  • Graft Rejection / prevention & control
  • Hepacivirus / genetics
  • Hepacivirus / isolation & purification
  • Hepatitis C / drug therapy
  • Hepatitis C / surgery*
  • Humans
  • Immunosuppressive Agents / classification
  • Immunosuppressive Agents / therapeutic use
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons / therapeutic use*
  • Liver Transplantation / pathology*
  • Middle Aged
  • RNA, Viral / blood
  • RNA, Viral / isolation & purification
  • Recombinant Proteins
  • Recurrence
  • Retrospective Studies
  • Ribavirin / therapeutic use
  • Transplantation, Homologous / pathology


  • Antiviral Agents
  • Immunosuppressive Agents
  • Interferon alpha-2
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Ribavirin
  • Interferons